Analysis of clinical factors and PDGFR-β in predicting prognosis of patients with clival chordoma

J Neurosurg. 2018 Dec 1;129(6):1429-1437. doi: 10.3171/2017.6.JNS17562.

Abstract

OBJECTIVEIn this study, the authors' aim was to research clinical features and prognostic factors in patients harboring clival chordomas and explore the relationship between platelet-derived growth factor receptor-β (PDGFR-β) expression and tumor invasion and prognosis of clival chordoma.METHODSA total of 242 patients were retrospectively analyzed. Clinical information, including extent of resection, Al-Mefty classification, postoperative complications, and postoperative radiotherapy, was reviewed. Kaplan-Meier analysis was used to estimate survival time. Immunohistochemical analysis, quantitative reverse transcription polymerase chain reaction, and Western blotting were used to measure the expression level of proteins or mRNA. Transwell assaying was performed to measure the invasive ability of the tumor cells.RESULTSAccording to the Al-Mefty classification, there were 37, 112, and 93 type I, II, and III tumors, respectively. Gross-total resection (GTR) was achieved in 86 cases (35.5%), subtotal resection (STR) in 63 cases (26.0%), and partial resection (PR) in 93 cases (38.4%). The 5-year progression-free survival (PFS) and overall survival (OS) rates in the GTR group were significantly higher than those in the non-total resection (NTR; i.e., STR and PR) group (p < 0.001). The 5-year PFS and OS rates for patients with type I tumors were significantly higher than those for patients harboring types II and III tumors (p < 0.001). In the NTR group, the median PFS and OS of patients with lower PDGFR-β expression were significantly longer than those of patients with higher PDGFR-β expression. Reduction of PDGFR-β suppressed the invasion ability of cells in vitro. In addition, reduction of PDGFR-β can obviously downregulate the expression levels of mammalian target of rapamycin (mTOR) or phospho-mTOR.CONCLUSIONSExtent of resection, Al-Mefty classification, primary tumor, postoperative radiotherapy, and PDGFR-β expression level are valuable prognostic factors in patients with clival chordomas. PDGFR-β could regulate invasion through the mTOR pathway in clival chordoma cells.

Keywords: GTR = gross-total resection; KPS = Karnofsky Performance Scale; NTR = non–total resection; OS = overall survival; PDGFR-β; PDGFR-β = platelet-derived growth factor receptor–β; PFS = progression-free survival; PR = partial resection; STR = subtotal resection; TMA = tissue microarray; classification; clival chordomas; degree of resection; invasion; mTOR = mammalian target of rapamycin; oncology; prognosis; radiotherapy; siRNA = small interfering RNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cell Line, Tumor
  • Child
  • Chordoma / metabolism
  • Chordoma / mortality
  • Chordoma / surgery*
  • Cranial Fossa, Posterior / metabolism
  • Cranial Fossa, Posterior / surgery*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Progression-Free Survival
  • Receptor, Platelet-Derived Growth Factor beta / metabolism*
  • Retrospective Studies
  • Skull Base Neoplasms / metabolism
  • Skull Base Neoplasms / mortality
  • Skull Base Neoplasms / surgery*
  • Survival Rate
  • Young Adult

Substances

  • Receptor, Platelet-Derived Growth Factor beta